The long term objective of the proposed work is to isolate and characterize the gene for the neurodegenerative genetic disorder spinocerebellar ataxia (SCA). The approach will be to first identify DNA markers that will enable the precise chromosomal localization of the SCA gene by linkage using two very large SCA families and the CEPH panel of reference families. The next step will be to use DNA markers that are close to the SCA gene by DNA cloning. Once the gene is isolated, it will be possible to determine the alteration that results in SCA. This will provide important insights into the development of this cerebellar degenerative disease and may also provide clues into the genetic basis of other neuronal degenerative diseases.